Atorvastatin Restores the Impaired Vascular Endothelium-dependent Relaxations Mediated by Nitric Oxide and Endothelium-derived Hyperpolarizing Factors but Not Hypotension in Sepsis

Abstract

Sepsis has been reported to impair endothelium-dependent vasodilations mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Although some studies demonstrate that statins can improve NO-mediated response in septic animals, little is known about its effect on the EDHF response. The present study examined the effects of atorvastatin pretreatment on sepsis-induced endothelial dysfunctions and hypotension in rats. Eighteen hours after the induction of sepsis by cecal ligation and puncture, thoracic aorta and second generation pulmonary arteries were isolated to examine acetylcholine-induced endothelium-dependent dilations mediated by NO and EDHF, respectively. The messenger RNA (mRNA) expression for endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was done by real-time polymerase chain reaction. NO was measured as nitrate/nitrite release using Griess method. Mean arterial pressure was measured by the invasive method. Sepsis significantly decreased (26%) the relaxation response to acetylcholine in the rat aorta. It also markedly inhibited the eNOS mRNA expression and acetylcholine-stimulated NO release in this vessel. Pretreatment of the rats with atorvastatin (10 mg/kg, orally) 48, 24, and 2 hours before induction of sepsis preserved acetylcholine-induced relaxation, eNOS mRNA expression, acetylcholine-stimulated NO release, and attenuated increase in the inducible NO synthase mRNA expression and basal NO production in the aorta. The maximal EDHF response mediated by acetylcholine was 25.30% +/- 3.00% in the pulmonary artery. Sepsis abolished this response but atorvastatin restored it (22.55% +/- 2.50%). Atorvastatin, however, failed to prevent sepsis-induced hypotension. These results suggest that atorvastatin can restore impaired endothelium-dependent vasodilations mediated by NO and EDHF but not hypotension in sepsis.

Erythropoietin Reverses Sepsis-Induced Vasoplegia to Norepinephrine Through Preservation of α1D-Adrenoceptor mRNA Expression and Inhibition of GRK2-Mediated Desensitization in Mouse Aorta

“…This observation is supported by a previous report from our laboratory in the rat sepsis model. 21 Results of the present study showed that EPO markedly preserved ACh-induced relaxation in the aorta from septic mice. This is consistent with the restoration of eNOS mRNA expression and reversal of decreased eNOS-derived NO release and tissue NO content in sepsis.…”

Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle

“…1A). A third group received daily supplementation with 10 mg/kg atorvastatin); this dose has been used in similar experimental protocols in rodent models by other groups [59,65]. Daily administration of atorvastatin partially blunted the increase in blood CLR levels introduced by the high CLR diet, as blood CLR levels in the statin-treated rats reached blood CLR levels that were intermediate between those from rats on normal chaw and rats receiving high CLR diet with placebo (Fig.…”

Coexistence of Lack of Clinical Manifestation of Oral Mycosis and Systemic Diseases in Edentulous Patients Using Removable Prosthetic Restorations

“…Besides, due to the inhibition of HMG-CoA reductase, which affects the synthesis of ergosterol, statins have shown a direct antifungal effect. Statins can also cause deletions in the yeast mitochondrial genome, impeding their development [ 25 ]. Additionally, even at clinically unachievable levels, synergy was observed between statins and fluconazole [ 24 ].…”